652 



NA TURE 



[October 24, 1907 



formaldehyde with some optically active constituent of 

 the chlorophyll granules. I shall give a more precise form 

 to this hypothesis if I say that I consider it probable that 

 the carbon dioxide itself enters into combination in this 

 manner, as there is reason to suppose that the proteins 

 offer sufficient opportunity for its fixation ; according to 

 Siegfried, even the simple amino-acids are capable of com- 

 bining with carbon dioxide. I am inclined to think that 

 this compound with carbon dioxide undergoes decomposition 

 into o.xygen and a reduction product, probably a derivative 

 of formaldehyde ; the condensation to sugar takes place 

 either in the original asymmetric comple.x or in one pro- 

 duced from it by a secondary change involving the separ- 

 ation of the formaldehyde and its re-association in some 

 other manner. It may be that the condensation takes 

 place directly or that intermediate compounds, biose or 

 glycerose, are formed. Thanks to the researches of 

 Marckwald, and especially those of Mackenzie, we are 

 acquainted with a whole series of asymmetric syntheses ; 

 no one of these, however, is half so complete as that 

 involved in the formation of sugar under natural conditions. 

 Indeed, it is obvious that if the natural process is to be 

 imitated in vitro, it will be necessary to alter the methods 

 hitherto adopted in every single detail ; difficult as this 

 may appear, it is not altogether impossible. 



But even if this be done successfully, the precise nature 

 of the assimilation process will not be finally elucidated. 

 It is to be expected that this will only be accomplished 

 when biological research, aided by improved analytical 

 methods, has succeeded in following the changes which 

 take place in the actual chlorophyll granules. 



The carbohydrates elaborated by the plant undergo com- 

 bustion to carbon dioxide and water in the animal body. 

 The change is easily effected by means of powerful 

 oxidising agents at the ordinary temperature ; the natural 

 process, however, must be a very different one, as in the 

 organism oxygen is conveyed to the carbohydrate by 

 oxidising enzymes, and doubtless many intermediate pro- 

 ducts are formed of which we know little at present. 



It would be easy to multiply examples ; but these two 

 are sufficient to demonstrate the incompleteness of the 

 explanation of biochemical processes deduced from the data 

 of organic chemistry. The service rendered to biology bv 

 chemical analysis and synthesis, which will be rendered 

 by it in even greater measure in the future, is to be sought 

 in other directions. 



The ultimate aim of biochemistry is to gain complete 

 insight into the unending series of changes which attend 

 plant and animal metabolism. To accomplish a task of 

 such magnitude, complete knowledge is required of each 

 individual chemical substance occurring in the cvcle of 

 changes and of analytical methods which will permit of 

 its recognition under conditions such as exist in the living 

 organism. As a matter of course, it is the office of organic 

 chemistry, especially of synthetic chemistry, to accumulate 

 this absolutely essential material. The chemical constitu- 

 tion of hundreds of carbon compounds which occur 

 naturally has already been determined, and their more 

 important properties have been established ; but far more 

 remains to be done. In proof of this, let me briefly direct 

 your attention to the three great classes of substances 

 which predominate in the living world : the fats, the 

 carbohydrates, and the proteins. 



It was established at least ninety years ago bv Chevreul, 

 in the course of his celebrated investigations into the 

 process of soap-making, that the fats can be decomposed 

 mto the glycerine discovered by Scheele and into fattv 

 acids ; but the relationship of these latter to one another 

 could not be understood until the conception of homo- 

 logous series had been evolved in organic chemistry. The 

 classical researches of Berthelot and the discovery of glvcol 

 by Wurtz were necessary preliminaries to the establish- 

 ment of the constitution of glycerine ; the final proof that 

 the fats nre neutral glvceric salts of the fattv acids was 

 first provided by Berthelot's synthesis. Synthetic methods 

 have made us acquainted with the mono- and di-glycerides 

 and also wiih mixed triglvcerides such as have frequentiv 

 been met with of late in 'nature. Nevertheless, the group 

 m which the natural fats are ranged is one in which there 

 are still many lacuna; and manv misstatements to be 

 corrected. 



NO. I9S2, VOL. 76] 



The problems afforded by the fats are simple, however, 

 in comparison with those connected with the carbohydrates. 

 The original subdivision of the group into mono-, di-, tri-, 

 and poly-saccharidcs has been justified in practice. Up to 

 the present time only the monosaccharides have been 

 studied satisfactorily from the point of view of their spatial 

 structure. The growth of our knowledge of the mono- 

 saccharides has proved in many ways to be of import- 

 ance in connection with biological inquiry, especially in 

 enabling us to penetrate the mystery of enzyme action 

 somewhat further. 



On contrasting the effects which emulsin and the 

 enzymes in yeast produce on the various glucosides pre- 

 pared by synthetic methods, I was led to conclude, not 

 only that there was a difference between the two series 

 of optical antipodes similar to that discovered by Pasteur 

 in the course of his studies of moulds, but that very slight 

 changes in configuration were sufficient to inhibit the 

 action of enzymes entirely. I was led by these observ- 

 ations to apply the simile of lock and key as an expression 

 of the close inter-relationship in configuration which obtains 

 between the enzyme and the substance which it attacks. 

 Similar results were obtained on investigating the 

 behaviour of the stereoisomeric he.xoses with yeast, the 

 fermentative power of which we now attribute to an 

 enzyme — E. Buchner's zymase. 



The experience gained with the glucosides became of 

 service in studying the polysaccharides. Another outcome 

 of the investigation has been the discovery of distinct 

 enzymes capable of attacking di- and tri-saccharides. .As 

 the result of these inquiries, I was able to formulate a 

 rule of general biological significance, namely, that the 

 alcoholic fermentation of a polysaccharide is necessarily 

 preceded by its hydrolysis by some particular enzyme. It 

 was shown, especiallv in the case of the invertase of 

 Monilia Candida, that it is not essential that the enzyme 

 should even be soluble in water. 



Unfortunately, but few successful syntheses of poly- 

 saccharides have been effected. It is most desirable, there- 

 fore, that better methods should be devised, as it is prob- 

 able that the attack on the dextrins, gums, and similar 

 undeciphered substances is most likely to be successful if 

 made from the synthetic side. It is to be expected that 

 biology would gain much by the discovery and utilisation 

 of such materials ; more, perhaps, than it has from the 

 study of the monosaccharides and of the glucosides pre- 

 pared by artificial means. 



The carbohydrate group is that in which use was first 

 made of enzymes as synthetic agents. Such syntheses 

 fascinate the imagination, as they approximate closely to 

 natural processes ; but I may point out that they cannot 

 take the place of purely chemical methods, as these latter 

 are so much more under our control and can be varied 

 in so many ways that we are in the position to produce 

 materials which it is quite impossible for the organised 

 world to furnish. Laboratory synthetic methods will be 

 indispensable for a long time to come, not only for pre- 

 parative purposes, but also as the means of elucidating 

 the structure of complex substances of natural origin. 



This contention is applicable to the proteins even more 

 than it is to the carbohydrates ; as they are among the 

 most complex substances produced in the living world and 

 are concerned in all the vital activities of the cell, a 

 complete comprehension of their nature must obviously 

 precede the full development of biological chemistry. We 

 distinguish to-day some forty to fifty natural proteins, 

 discovered by the joint labours of chemists and physio- 

 loaists ; but it is to be expected that as the methods of 

 differentiating and separating them are improved, the!' 

 number will be lai gely increased. 



At present the majority are known only in an 

 amorphous form ; some important terms of the group, 

 however, such as oxvhaemoglobin, e^^ albumin and the 

 albumin of horse serum, excelsin from the Brazil nut, and 

 the edestins from other plant seeds, have been obtained 

 in definite crystals ; but, unfortunately, it cannot be 

 decided from their crystalline appearance whether these 

 products are definite substances, as the tendcncv to form 

 mixed crystals is the greater the more complicated the 

 molecule. Examples in point are afforded by the aniline 

 dyes, the higher fatty acids, and the purine compounds ; 



